Effects of SCH-23390 and raclopride on cocaine discrimination in male and female Wistar rats

Male and female rats were trained to discriminate 10.0 mg/kg cocaine from saline in a two-lever discrimination task. Injection-appropriate responding was reinforced by food pellet presentation on a tandem random-interval 30-s fixed-ratio 10 schedule. Generalization testing was conducted in extinction 10 min following an injection of saline, 1.0, 3.0, 5.6, or 10.0 mg/kg cocaine. No differences in the generalization gradients and ED(50)s were observed between male and female rats. Following the determination of the cocaine generalization gradient, the dopamine D(1) antagonist SCH-23390 (0.01-0.10 mg/kg) and the dopamine D(2) antagonist raclopride (0.1-1.6 mg/kg) were administered (independently) prior to the injection of the training dose of cocaine (10.0 mg/kg). Cocaine-antagonism tests were conducted in extinction. It was found, for each dopamine antagonist, that as the dose increased, the percentage of cocaine-appropriate responding decreased. No sex differences were observed between these generalization gradients.